AUTHOR=Pihlström Sandra , Richardt Sampo , Määttä Kirsi , Pekkinen Minna , Olkkonen Vesa M. , Mäkitie Outi , Mäkitie Riikka E. 

TITLE=SGMS2 in primary osteoporosis with facial nerve palsy

JOURNAL=Frontiers in Endocrinology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1224318

DOI=10.3389/fendo.2023.1224318

ISSN=1664-2392

ABSTRACT=<p>Pathogenic heterozygous variants in <italic>SGMS2</italic> cause a rare monogenic form of osteoporosis known as calvarial doughnut lesions with bone fragility (CDL). The clinical presentations of <italic>SGMS2</italic>-related bone pathology range from childhood-onset osteoporosis with low bone mineral density and sclerotic doughnut-shaped lesions in the skull to a severe spondylometaphyseal dysplasia with neonatal fractures, long-bone deformities, and short stature. In addition, neurological manifestations occur in some patients. <italic>SGMS2</italic> encodes sphingomyelin synthase 2 (SMS2), an enzyme involved in the production of sphingomyelin (SM). This review describes the biochemical structure of SM, SM metabolism, and their molecular actions in skeletal and neural tissue. We postulate how disrupted SM gradient can influence bone formation and how animal models may facilitate a better understanding of <italic>SGMS2</italic>-related osteoporosis.</p>